Sample Size in Clinical Cardioprotection Trials Using Myocardial Salvage Index, Infarct Size, or Biochemical Markers as Endpoint

J Am Heart Assoc. 2016 Mar 9;5(3):e002708. doi: 10.1161/JAHA.115.002708.


Background: Cardiac magnetic resonance (CMR) can quantify myocardial infarct (MI) size and myocardium at risk (MaR), enabling assessment of myocardial salvage index (MSI). We assessed how MSI impacts the number of patients needed to reach statistical power in relation to MI size alone and levels of biochemical markers in clinical cardioprotection trials and how scan day affect sample size.

Methods and results: Controls (n=90) from the recent CHILL-MI and MITOCARE trials were included. MI size, MaR, and MSI were assessed from CMR. High-sensitivity troponin T (hsTnT) and creatine kinase isoenzyme MB (CKMB) levels were assessed in CHILL-MI patients (n=50). Utilizing distribution of these variables, 100 000 clinical trials were simulated for calculation of sample size required to reach sufficient power. For a treatment effect of 25% decrease in outcome variables, 50 patients were required in each arm using MSI compared to 93, 98, 120, 141, and 143 for MI size alone, hsTnT (area under the curve [AUC] and peak), and CKMB (AUC and peak) in order to reach a power of 90%. If average CMR scan day between treatment and control arms differed by 1 day, sample size needs to be increased by 54% (77 vs 50) to avoid scan day bias masking a treatment effect of 25%.

Conclusion: Sample size in cardioprotection trials can be reduced 46% to 65% without compromising statistical power when using MSI by CMR as an outcome variable instead of MI size alone or biochemical markers. It is essential to ensure lack of bias in scan day between treatment and control arms to avoid compromising statistical power.

Keywords: acute myocardial infarction; biochemical markers; cardioprotection; myocardial salvage index; sample size.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bias
  • Biomarkers / blood
  • Computer Simulation
  • Creatine Kinase, MB Form / blood*
  • Endpoint Determination / methods*
  • Humans
  • Magnetic Resonance Imaging*
  • Myocardial Infarction / blood
  • Myocardial Infarction / etiology
  • Myocardial Infarction / pathology
  • Myocardial Infarction / prevention & control*
  • Myocardium / metabolism*
  • Myocardium / pathology*
  • Percutaneous Coronary Intervention / adverse effects*
  • Predictive Value of Tests
  • Reperfusion Injury / blood
  • Reperfusion Injury / etiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control*
  • Reproducibility of Results
  • Sample Size*
  • Time Factors
  • Treatment Outcome
  • Troponin T / blood*


  • Biomarkers
  • Troponin T
  • Creatine Kinase, MB Form